The bacteria Streptococcus pneumoniae is the leading cause of ear infections, sinus infections, and meningitis in children. Rhesus monkeys are also susceptible to infection with Streptococcus pneumoniae bacteria. The immune response to Streptococcus pneumoniae vaccines in monkeys is similar to humans. Several potential vaccines to protect humans against Streptococcus pneumoniae infections have been developed. The purpose of this project was to study the ability of three different adjuvants combined with an investigational pneumococcal vaccine against seven types of pneumococcus to protect infant rhesus monkeys from colonization of the nose with pneumococcus type 14. Sixteen infant rhesus monkeys (four groups of four) were immunized at 2, 4, and 6 months of age with a seven component pneumococcal vaccine; one group (control group) did not receive vaccine, the other three groups received vaccine with either alum, alum plus MPL, or alum plus QS-21. Blood was obtained at the time vaccine was administered and 1 month after the third dose of vaccine. The immune response to each of the seven types of pneumococcus included in the vaccine was evaluated. The vaccine was immunogenic; alum alone gave the lowest response, alum plus MPL gave the highest response for serotypes 6B, 9V, and 14, and alum plus QS-21 gave the highest response for serotypes 4, 18C, 19F, and 23F. At nine months of age the animals were challenged with increasing amounts of Streptococcus pneumoniae type 14. All four animals in the control group were colonized with low amounts of Streptococcus pneumoniae. Only four of twelve animals who were vaccinated became colonized following pneumococcal challenge. This study demonstrates that MPL and QS-21 adjuvants are superior to alum alone in inducing an immune response to pneumococcal vaccine. Pneumococcal vaccine decreased nasopharyngeal colonization in the juvenile monkeys. Based on the positive results from this study, clinical trials in humans should be considered with both MPL and QS-21 adjuvants.